Microcantilevers can be utilized in biophysical and biochemical studies to determine energy changes as indications of biochemical reactions in a medium. There is a great interest in developing ultra-miniature probes and assays that require very small volumes of sampled media for accurate qualitative and quantitative analysis of biochemical reactions and these assays can be performed using a microcantilever bound substrate.
In Thundat et al., U.S. Pat. No. 5,719,324, a piezoelectric transducer is disclosed that is fabricated with a cantilever having a spring element treated with a chemical which reacts with a specific vapor phase chemical. An oscillator means maintains a resonant vibrational frequency during detection of a chemical, with changes in resonant frequency indicating amounts of targeted chemical detected in the monitored atmosphere. Alternatively, the rate of cantilever bending is monitored to indicate the target chemical concentration.
In Wachter et al., U.S. Pat. No. 5,445,008, a mass microsensor is disclosed that is fabricated with a microcantilever that oscillates due to a piezoelectric transducer, with a chemical coating on the microcantilever that absorbs a targeted chemical from the monitored atmosphere. The resonant frequency of the microcantilever is analyzed to determine changes that indicate amounts of targeted chemical detected in the monitored atmosphere.
In Marcus et al., U.S. Pat. No. 5,475,318, a microprobe is disclosed that includes a microcantilever, a base, a probe tip projecting from the base, and a heating element that heats the probe tip, which comes into contact with a material to be investigated.
In Hafeman, U.S. Pat. No. 4,963,815, a device and method is provided for determining an analyte by measuring a redox potential-modulated photoinducing electrical signal from an electronically conducting layer on a semiconductor device.
In Kolesar, U.S. Pat. No. 4,549,427, a chemical nerve agent detector is disclosed that includes a transducer having two microcantilever oscillators. The active microcantilever of the two microcantilevers has a chemically selective substance that absorbs chemical nerve agents from the atmosphere, with modifications in the oscillation of the active microcantilever, and comparisons are made between the frequency of the active cantilever and the reference cantilever.
The above described methods and devices of measuring chemical and micromechanical parameters are not directed towards immunoassays which can detect the binding of a few molecules upon a substrate. The present invention describes a novel and sensitive technique which measures adsorption-induced forces for detecting proteins, other biopolymers, nucleic acid sequences, and micro-organisms in a gas or liquid medium using microcantilever.